TY - JOUR
T1 - Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease
AU - Nakao, Isao
AU - Kanaji, Sachiko
AU - Ohta, Shoichiro
AU - Matsushita, Hidetomo
AU - Arima, Kazuhiko
AU - Yuyama, Noriko
AU - Yamaya, Mutsuo
AU - Nakayama, Katsutoshi
AU - Kubo, Hiroshi
AU - Watanabe, Mika
AU - Sagara, Hironori
AU - Sugiyama, Kumiya
AU - Tanaka, Hiroyuki
AU - Toda, Shuji
AU - Hayashi, Hiroaki
AU - Inoue, Hiromasa
AU - Hoshino, Tomoaki
AU - Shiraki, Aya
AU - Inoue, Makoto
AU - Suzuki, Koichi
AU - Aizawa, Hisamichi
AU - Okinami, Satoshi
AU - Nagai, Hiroichi
AU - Hasegawa, Mamoru
AU - Fukuda, Takeshi
AU - Green, Eric D.
AU - Izuhara, Kenji
PY - 2008/5/1
Y1 - 2008/5/1
N2 - Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.
AB - Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.
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U2 - 10.4049/jimmunol.180.9.6262
DO - 10.4049/jimmunol.180.9.6262
M3 - Article
C2 - 18424749
AN - SCOPUS:44449127236
VL - 180
SP - 6262
EP - 6269
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -